Type 2 diabetes mellitus is a clinically and genetically heterogeneous group of syndromes characterized by elevated blood glucose levels. It occurs because the insulin produced by the β (beta) cells of the pancreas is either insufficient or ineffectively utilized by target tissues, resulting in high levels of glucose in the blood. Post-prandial peaks (a rise of glucose in the body after a meal), which usually result from a high carbohydrate diet, contribute to the high blood glucose levels. Complications that surface from diabetes can usually be traced back to excessive sugar levels in the blood over a period of many years.
The progression of type 2 diabetes is often characterised as follows. At first a slow but progressive increase in insulin resistance develops. This implies that insulin production by the pancreas is normal during the early stages of the disease, but the ability of insulin to increase glucose uptake is reduced. The reduced insulin sensitivity in the early stages of the disease is usually compensated by an increased release of insulin by the pancreas. However, after several years the pancreas no longer responds properly to glucose ingestion and the reduced insulin sensitivity is accompanied by a suboptimal insulin production. The resulting hyperglycaemia (high blood glucose level) leads to a rapid disabilitating progression of the disease and the necessity to start using oral medication and finally exogenous insulin therapy.
The abnormally high levels of glucose in the blood may contribute to various micro- and macrovascular complications, including cardiovascular disease, retinopathy, nephropathy and neuropathy. Serious health complications resulting from these high glucose levels include eye, heart, kidney, and nerve damage.
The key to fighting diabetes is through monitoring and controlling blood sugar levels. If patients conscientiously monitor and control their blood sugar level at an early stage, they may delay or prevent many complications associated with the disorder. A proper diet and exercise can help people with diabetes to maintain healthy blood glucose levels. However, when diet and exercise are inadequate to control diabetes, medication is required. At this stage treatment can still rely on the use of oral anti-diabetic drugs alone, i.e. exogenous insulin therapy is not yet necessary.
In principle three classes of oral anti-diabetes drugs are available, namely the “blocker” class, the “stimulator” class and the “sensitizer” class. The “blocker” class of oral anti-diabetes agents has been shown to delay or prevent further development of the disease. Examples of this class of agents are the so-called alpha-glucosidase inhibitors, which act by delaying the absorption of glucose from the ingested carbohydrates. The “stimulator” class of oral anti-diabetic agents stimulate the production of insulin by the pancreas. Examples of the “stimulator” class are sulfonylureas, which are known to be effective to stimulate secretion of insulin. The “sensitizer” class of oral anti-diabetic agents help to use glucose more efficiently or to make tissue cells more sensitive to insulin. Examples of pharmaceutical “insulin sensitizers” are biguanides (such as Metformin (e.g. Glucophage®) and thiazolidinediones (such as Pioglitazone (e.g. Actos®) and Rosiglitazone (e.g. Avandia®). Not surprisingly several of these oral anti-diabetic drugs have undesirable side effects. For example, adverse effects of sulphonylurea antidiabetic agents include hypoglycaemia, gastro-intestinal disturbances and hypersensitivity reactions. Adverse effects of the insulin sensitiser biguanide include gastrointestinal disturbances and lactic acidosis.
Milder insulin sensitizing effects can be obtained with a number of natural compounds. The obvious advantage of such natural insulin sensitizers is that they are convenient and safe to use. These natural insulin sensitizers can, for example, be added to our regular diet, or be added to dietary supplements and functional foods. One of these natural insulin sensitizers is chromium. Chromium is a trace mineral that is essential for normal insulin function. Dietary studies indicate that most people in the U.S. and other industrialized countries do not consume enough chromium, and deficiencies appear to be even more common in diabetic people. Many clinical studies support the benefits and safety of chromium supplementation in diabetic people. Supplemental chromium is known to lower blood insulin levels, improve glucose tolerance and decrease haemoglobin glycosylation in people with type 2 diabetes. Chromium also helps maintain healthy blood lipid levels, in particular triglycerides and HDL cholesterol. Experts, such as Richard Anderson, Ph.D. from the U.S. Dept. of Agriculture at the Beltsville Human Nutrition Research Center, recommend chromium supplementation in daily amounts of 200-1000 micrograms. Clinical studies show that in particular the organic or chelated forms, such as chromium polynicotinate, picolinate, glycine-niacin chelate, GTF chromium and chromium yeast are effective. Furthermore it has been shown that combinations of chromium and biotin (i.e. Vitamin B8) act synergistically.
Vanadium is another trace element involved in promoting normal insulin function. Some studies have shown that vanadium supplied as vanadyl sulfate can improve glucose tolerance in type 2 diabetics. Supplementation with up to 100 micrograms/day is safe, and will satisfy the body's nutritional vanadium needs including the requirement for insulin and glucose metabolism.
Niacin is another B-vitamin of special importance to diabetes. 100 milligrams/day of niacin has been shown to improve glucose tolerance and fasting blood glucose in diabetics when co-supplemented with chromium.
Fenugreek (Trigonella foenum-graecum) is a herb that is native to South East Europe, North Africa and Western Asia. The herb has been shown to be beneficial in the treatment of both type 1 and type 2 diabetes, and is thought to help control blood sugar in addition to lowering serum cholesterol levels. A dose as small as 15 mg may help to control fasting blood sugar levels as well as control sudden peaks in blood sugar following meals [‘Gales Encyclopedia of Alternative Medicine’, Turner J.].
Banaba Leaf Extract is a newcomer among standardized diabetes herbs and is currently sold under the trade name “Glucosol.” The active compound in Glucosol, corosolic acid, has been shown to promote the transport of blood glucose into cells. Glucosol is standardized to provide a minimum of 1% corosolic acid. The extract was found to be well-tolerated and safe in human and animal studies. Compared to other herbal extracts used be people with diabetes, Glucosol offers the advantage that it can lower blood glucose in diabetic people without causing hypoglycaemia. Also, the clinically effective dose is only 32-48 milligrams daily. A series of recent and still unpublished clinical studies conducted in 1999 by Dr. W. Judy at the Southeastern Institute of Biomedical Research (Bradenton, Fla.), showed significant benefits of Glucosol when taken daily for 30 days at 32 and 48 milligrams per day. One of these studies was a randomized, double-blind crossover study with 12 diabetic subjects taking 48 milligrams of the extract. Glucosol lowered fasting blood glucose in people with type 2 diabetes, and the effect was sustained for several weeks even after discontinuation of the supplement. Study reports are available from the manufacturer (Soft Gel Technologies, Inc.) at their website (www.glucosol.com/glucosol/default.htm).
Pterostilbene, a compound found in grapes, has been identified by the USDA, and is a phytoalexin that is produced by the vines in response to stressful conditions. Studies from the Department suggest that the compound is capable of reducing blood sugar levels by up to 42%, an effect comparable to that of the antidiabetic drug metformin. Unfortunately for wine drinkers, however, it is unlikely that the compound is present in wines, due to its instability to light and air.
The potential for cinnamon in treating type 2 diabetes was first noted in August 2000. The news came from an unpublished study demonstrating that the active compound present in cinnamon, methylhydroxy chalcone polymer (MHCP), could normalise very high glucose levels in diabetic mice. Other experiments suggested this antidiabetic effect of MHCP is due to its ability to increase the cell's response to insulin, and it has been estimated that sensitivity to insulin raises by around 20 fold on administration of the chemical. Following the release of the information, researchers at the US Agricultural Research Service recommended that diabetics consume between one-quarter and one teaspoon of cinnamon per day, either alone or in foods.
Ginsenoside Re, a compound found in the ginseng berry, has been shown to be beneficial in the treatment of diabetes and obesity, helping to normalise blood sugar levels, improve insulin sensitivity and aid weight loss. Researchers, from the University of California, tested the effects of the berry on 2 groups of mice (one nondiabetic set, and a second bred to be diabetic). The berries can help to normalize blood sugar levels, improve insulin sensitivity, lower cholesterol and aid weight loss. Ginsenoside Re has been found to be one of the compounds in the berries responsible for the improved insulin sensitivity [BBC News, Monday, 10 Apr., 2000; http://news.bbc.co.uk/hi/english/health/newsid—2004000/2004255.stm].
Within the scope of the present application the term “insulin sensitizer” or “insulin sensitizing agent” refers to a compound, preferably a pharmaceutical compound or preferably a natural compound, that will lower blood glucose levels by increasing the responsiveness of the tissues to preferably insulin.
Insulin sensitizers have been shown to be effective in lowering blood glucose levels by increasing the responsiveness of target tissues to insulin. However, as the disease progresses, type 2 diabetic patients gradually loose their ability to produce sufficient insulin. This decrease in insulin production slowly diminishes the effectiveness of the insulin sensitizers, so at a certain point these patients are forced to change from natural and relatively harmless insulin sensitizers to pharmaceutical insulin sensitizers such as biguanides or thiazolidinediones and eventually drastic measures like insulin injections are required to lower blood glucose levels.
To prevent or postpone this need for pharmaceutical insulin sensitizers and finally insulin injections of diabetes type 2, there is a need for a composition that results in an effective lowering of blood glucose.